Skip to main content
NCBI home page
BMJ Clinical Evidence logoLink to BMJ Clinical Evidence
. 2013 Dec 11;2013:1606.

Pelvic inflammatory disease

Jonathan D C Ross 1
PMCID: PMC3859178  PMID: 24330771

Abstract

Introduction

Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the US, and is diagnosed in approximately 1% of women aged 16 to 45 years consulting their GP in England and Wales.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: How do different antimicrobial regimens compare when treating women with confirmed pelvic inflammatory disease? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up to date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 13 RCTs or systematic reviews of RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, different durations, different regimens) and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk).

Key Points

Pelvic inflammatory disease (PID) is caused by infection of the upper female genital tract, and is often asymptomatic.

  • PID is the most common gynaecological reason for admission to hospital in the US, and is diagnosed in 1.1% of women aged 16 to 45 years consulting their GP in England and Wales.

  • Epithelial damage from infections such as Chlamydia trachomatis or Neisseria gonorrhoeae may allow opportunistic infection from many other bacteria.

  • About 20% of women with PID become infertile, 40% develop chronic pain, and 1% of women who conceive have an ectopic pregnancy.

  • Spontaneous resolution of symptoms may occur in some women.

  • Empirical treatment is started as soon as the diagnosis of PID is suspected to minimise the risk of sequelae such as tubal obstruction and infertility.

  • The positive predictive value of clinical diagnosis is 65% to 90% compared with laparoscopy, and observational studies suggest that delaying treatment by three days may impair fertility.

  • The absence of infection from the lower genital tract does not exclude a diagnosis of PID.

Oral antibiotics are likely to be beneficial, and are associated with the resolution of symptoms and signs of pelvic infection, but we don't know which antibiotic regimen is best.

  • Clinical and microbiological cure rates of 88% to 100% have been reported after oral antibiotic treatment.

  • The risks of tubal occlusion and infertility depend on severity of infection before treatment. Clinical improvement following treatment may not necessarily translate into improved long-term fertility .

Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility in women with mild to moderate PID, with fewer adverse effects. However, we don't know the optimal duration of treatment.

Women at high risk for PID include those with prior infection with C trachomatis or N gonorrhoeae, young age at onset of sexual activity, unprotected sexual intercourse with multiple partners, and prior history of PID. Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable. We don't know whether prophylactic antibiotics before IUD insertion reduce these risks.

Clinical context

General background

Pelvic inflammatory disease (PID) is a common cause of morbidity in young women, usually occurring as a consequence of sexually transmitted infection. Chlamydia and gonorrhoea are the commonest recognised causes but in the majority of cases no pathogen is identified. Treatment is with broad spectrum antibiotics which are associated with high rates of short term improvement, but despite treatment there is an increased risk of tubal damage leading to chronic pelvic pain and infertility.

Focus of the review

The main focus of this review is on which antimicrobial regimens are most effective in the treatment of pelvic inflammatory disease and how long treatment should be given for. The review also assesses the rate of adverse events associated with different treatment regimens, and whether prophylactic antibiotics prior to the insertion of an intrauterine contraceptive device are effective in preventing PID. The timing of when to start antibiotics (before or after the results of microbiology test are available) is not assessed because of lack of evidence found in the previous version of this Clinical Evidence overview and current expert opinion that treatment should not be delayed.

Comments on evidence

We identified a large number of randomised controlled trials comparing different treatment regimens for pelvic inflammatory disease, but the majority were small and of low quality. A small number of large well conducted trials and one systematic review were available. Specific limitations included short term follow up limited to a few weeks, and difficulties in making an objective diagnosis of pelvic inflammatory disease.

Search and appraisal summary

The update literature search for this review was carried out from the date of the last search, May 2007 to September 2013. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the review, please see the Methods section. Searching of electronic databases retrieved 97 studies. After de-duplication and removal of conference abstracts, 35 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 27 studies and the further review of 8 full publications. Of the 8 full articles evaluated, 1 systematic review and 3 RCTs were added at this update.

About this condition

Definition

Pelvic inflammatory disease (PID) is inflammation and infection of the upper genital tract in women, typically involving the uterus and adnexae.Mild-to-moderate PID is defined as the absence of a tubo-ovarian abscess. Severe disease is defined as severe systemic symptoms or the presence of tubo-ovarian abscess.

Incidence/ Prevalence

The exact incidence of PID is unknown because the disease cannot be diagnosed reliably from clinical symptoms and signs. Direct visualisation of the fallopian tubes by laparoscopy is the best single diagnostic test, but it is invasive, lacks sensitivity, and is not used routinely in clinical practice. PID is the most common gynaecological reason for admission to hospital in the US, accounting for 18/10,000 recorded hospital discharges. A diagnosis of PID is made in 1.1% of women aged 16 to 45 years attending their primary-care physician in England and Wales. However, because most PID is asymptomatic, this figure under-estimates the true prevalence. A crude marker of PID in resource-poor countries can be obtained from reported hospital admission rates, where it accounts for 17% to 40% of gynaecological admissions in sub-Saharan Africa, 15% to 37% in Southeast Asia, and 3% to 10% in India.

Aetiology/ Risk factors

Factors associated with PID mirror those for STDs — young age, reduced socioeconomic circumstances, lower educational attainment, and recent new sexual partner. Women considered at high risk for PID include those with prior infection with chlamydia or gonorrhoea, young age at onset of sexual activity, unprotected sexual intercourse with multiple partners, and prior history of PID. Infection ascends from the cervix, and initial epithelial damage caused by bacteria (especially Chlamydia trachomatis and Neisseria gonorrhoeae) may allow the opportunistic entry of other organisms. Many different microbes, including Mycoplasma genitalium and anaerobes, may be isolated from the upper genital tract. The spread of infection to the upper genital tract can be increased by instrumentation of the cervix, but reduced by barrier methods of contraception, levonorgestrel implants, and by oral contraceptives compared with other forms of contraception.

Prognosis

PID has a high morbidity; about 20% of affected women become infertile, 40% develop chronic pelvic pain, and 1% of those who conceive have an ectopic pregnancy (see table 1 ). Uncontrolled observations suggest that clinical symptoms and signs resolve in a significant proportion of untreated women.

Table 1.

RCTs comparing outpatient versus inpatient antibiotic treatment for PID at different follow-up periods (see text).

Ref Population Recurrence Chronic pelvic pain Infertility Ectopic pregnancy
  831 women with mild to moderate PID; 808 followed up to 35 months; inpatients v outpatients 12% v 17%; OR 0.69, 95% CI 0.43 to 1.09 34% v 30%; OR 1.24, 95% CI 0.87 to 1.77 18.4% v 17.9%; OR 1.32, 95% CI 0.86 to 2.04 1.0% v 0.3%; OR 3.66, 95% CI 0.40 to 33.12
  As above; 541 followed up to 84 months; inpatients v outpatients 18% v 24%; OR 0.71, 95% CI 0.48 to 1.05 41% v 45%; OR 1.21, 95% CI 0.87 to 1.67 17% v 21%; OR 0.88, 95% CI 0.59 to 1.32 1.2% v 0.2%; OR 4.91, 95% CI 0.57 to 42.25
Open in a new tab

PID, pelvic inflammatory disease

Aims of intervention

To alleviate the pain and systemic malaise associated with infection; to achieve microbiological cure; to prevent development of permanent tubal damage with associated sequelae, such as chronic pelvic pain, ectopic pregnancy, and infertility; and to prevent the spread of infection to others, with minimal adverse effects.

Outcomes

Cure rate (includes clinical cure rate; microbiological cure of the upper genital tract; resolution of acute symptoms and signs); symptom severity (includes reduction of chronic pelvic pain); rate of ectopic pregnancy; fertility (includes pregnancy [other than ectopic]); rate of transmission to others; recurrence; quality of life; and adverse effects of treatment; in question on routine antibiotic prophylaxis: rate of PID.

Methods

Clinical Evidence search September 2013. The following databases were used to identify studies for this systematic review: Medline 1966 to September 2013, Embase 1980 to September 2013, and The Cochrane Database of Systematic Reviews, issue 2, 2013 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Titles and abstracts identified by the initial search, run by an information specialist, were first assessed against predefined criteria by an evidence scanner. Full texts for potentially relevant studies were then assessed against predefined criteria by an evidence analyst. Studies selected for inclusion were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were: published systematic reviews and RCTs, at least single-blinded, and containing 20 or more individuals of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs, where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA, the EMA, and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Pelvic inflammatory disease.

Important outcomes Cure rate, Fertility, Quality of life, Rate of ectopic pregnancy, Rate of PID, Rate of transmission to others, Recurrence, Symptom severity
Studies (Participants) Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment
How do different antimicrobial regimens compare when treating women with confirmed pelvic inflammatory disease?
at least 35 RCTs (at least 4289 women) Cure rate Different antibiotics versus each other 4 –2 0 –1 0 Very low Quality points deducted for incomplete reporting of results and for poor quality studies; directness point deducted for unclear disease severity/regimens used
1 (120) Symptom severity Different antibiotics versus each other 4 –1 0 –1 0 Low Quality point deducted for sparse data; directness point deducted for short follow-up
1 (460) Recurrence Different antibiotics versus each other 4 –1 0 –1 0 Low Quality points deducted for incomplete reporting of results; directness point deducted due to short-term follow-up (unclear whether recurrence or relapse)
2 (321) Cure rate Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for incomplete reporting of results. Directness point deducted for inclusion of oral antibiotics in parenteral arm
1 (831) Symptom severity Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for no statistical assessment. Directness point deducted for inclusion of intramuscular injection in outpatient arm and oral antibiotics in parenteral arm
1 (831) Rate of ectopic pregnancy Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for no statistical assessment. Directness point deducted for inclusion of intramuscular injection in outpatient arm
1 (831) Fertility Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for no statistical assessment for some outcomes. Directness point deducted for inclusion of intramuscular injection in outpatient arm
1 (831) Recurrence Oral antibiotics versus parenteral antibiotics 4 –1 0 –1 0 Low Quality point deducted for no statistical assessment. Directness point deducted for inclusion of intramuscular injection in outpatient arm
What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before IUD insertion?
6 (5797) Rate of PID Antibiotic prophylaxis before IUD insertion versus no antibiotic prophylaxis (in women at low risk) 4 0 0 –1 0 Moderate Directness point deducted for small number of events
Open in a new tab

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Moderate-quality evidence

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

References

  • 1.Ness RB, Soper DE, Holley RL, et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am J Obstet Gynecol 2002;186:929–937. [DOI] [PubMed] [Google Scholar]
  • 2.Morcos R, Frost N, Hnat M, et al. Laparoscopic versus clinical diagnosis of acute pelvic inflammatory disease. J Reprod Med 1993;38:53–56. [PubMed] [Google Scholar]
  • 3.Metters JS, Catchpole M, Smith C, et al. Chlamydia trachomatis: summary and conclusions of CMO's expert advisory group. London: Department of Health, 1998. [Google Scholar]
  • 4.Centers for Disease Control. 2010 guidelines for treatment of sexually transmitted diseases. Bethesda, Maryland: CDC, 2010. http://www.cdc.gov/std/treatment/2010/default.htm (last accessed 1 November 2013). [Google Scholar]
  • 5.Sutton MY, Strenberg M, Zaida A, et al. Trends in pelvic inflammatory disease hospital discharges and ambulatory visits, United States 1985–2001. Sex Trans Dis 2005;32:778–784. [DOI] [PubMed] [Google Scholar]
  • 6.French CE, Hughes G, Nicholson A, et al. Estimation of the rate of pelvic inflammatory disease diagnoses: trends in England, 2000–2008. Sex Transm Dis 2011;38:158–162. [DOI] [PubMed] [Google Scholar]
  • 7.Velebil P, Wingo PA, Xia Z, et al. Rate of hospitalization for gynecologic disorders among reproductive-age women in the United States. Obstet Gynecol 1995;86:764–769. [DOI] [PubMed] [Google Scholar]
  • 8.Kani J, Adler MW. Epidemiology of pelvic inflammatory disease. In: Berger GS, Westrom L, eds. Inflammatory disease. New York: Raven Press, 1992. [Google Scholar]
  • 9.Simms I, Catchpole M, Brugha R, et al. Epidemiology of genital Chlamydia trachomatis in England and Wales. Genitourin Med 1997;73:122–126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Grodstein F, Rothman KJ. Epidemiology of pelvic inflammatory disease. Epidemiology 1994;5:234–242. [DOI] [PubMed] [Google Scholar]
  • 11.Bevan CD, Johal BJ, Mumtaz G, et al. Clinical, laparoscopic and microbiological findings in acute salpingitis: report on a United Kingdom cohort. Br J Obstet Gynaecol 1995;102:407–414. [DOI] [PubMed] [Google Scholar]
  • 12.Ross JD. Is Mycoplasma genitalium a cause of pelvic inflammatory disease? Infect Dis Clin North Am 2005;19:407–413. [DOI] [PubMed] [Google Scholar]
  • 13.Wolner-Hanssen P, Eschenbach DA, Paavonen J, et al. Association between vaginal douching and acute pelvic inflammatory disease. JAMA 1990;263:1936–1941. [DOI] [PubMed] [Google Scholar]
  • 14.Jacobson L, Westrom L. Objectivized diagnosis of acute pelvic inflammatory disease. Diagnostic and prognostic value of routine laparoscopy. Am J Obstet Gynecol 1969;105:1088–1098. [DOI] [PubMed] [Google Scholar]
  • 15.Kelaghan J, Rubin GL, Ory HW, et al. Barrier-method contraceptives and pelvic inflammatory disease. JAMA 1982;248:184–187. [PubMed] [Google Scholar]
  • 16.Wolner-Hanssen P, Eschenbach DA, Paavonen J, et al. Decreased risk of symptomatic chlamydial pelvic inflammatory disease associated with oral contraceptive use. JAMA 1990;263:54–59. [DOI] [PubMed] [Google Scholar]
  • 17.Sivin I. Risks and benefits, advantages and disadvantages of levonorgestrel-releasing contraceptive implants. Drug Saf 2003;26:303–335. [DOI] [PubMed] [Google Scholar]
  • 18.Ness RB, Trautmann G, Richter HE, et al. Effectiveness of treatment strategies of some women with pelvic inflammatory disease: a randomized trial. Obstet Gynecol 2005;106:573–580. [Erratum in Obstet Gynecol 2006;107:1423–1425] [DOI] [PubMed] [Google Scholar]
  • 19.Meads C, Knight T, Hyde C, et al. The clinical effectiveness and cost effectiveness of antibiotic regimens for pelvic inflammatory disease, 2004. West Midlands Health Technology Assessment Collaboration. [Google Scholar]
  • 20.Ross JD, Cronje HS, Paszkowski T, et al. Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial. Sex Transm Infect 2006;82:446–451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Heystek M, Ross JDC. A randomized double-blind comparison of moxifloxacin and doxycycline/metronidazole/ciprofloxacin in the treatment of acute, uncomplicated pelvic inflammatory disease. Int J STD AIDS 2009;20:690–695. [DOI] [PubMed] [Google Scholar]
  • 22.Judlin P, Liao Q, Liu Z, et al. Efficacy and safety of moxifloxacin in uncomplicated pelvic inflammatory disease: the MONALISA study. BJOG 2010;117:1475–1484. [DOI] [PubMed] [Google Scholar]
  • 23.Savaris RF, Teixeira LM, Torres TG, et al. Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstet Gynecol 2007;110:53–60. [DOI] [PubMed] [Google Scholar]
  • 24.Hoyme UBA. Quinolones in the treatment of uncomplicated salpingitis: Ofloxacin/metronidazole vs. gentamicin/clindamicin. Archives of Gynecology and Obstetrics 1993;254:607–608. [Google Scholar]
  • 25.Dublanchet, M. Comparative evaluation of clindamycin/gentamicin and cefoxitin/doxycycline for treatment of pelvic inflammatory disease: A multi-center trial. The European Study Group. Acta Obstet Gynecol Scand 1992;71:129–134. [DOI] [PubMed] [Google Scholar]
  • 26.Hemsell DL, Little BB, Faro S, et al. Comparison of three regimens recommended by the Centers for Disease Control and Prevention for the treatment of women hospitalized with acute pelvic inflammatory disease. Clin Infect Dis 1994;19:720–727. [DOI] [PubMed] [Google Scholar]
  • 27.Walters MDG. A randomized comparison of gentamicin-clindamycin and cefoxitin-doxycycline in the treatment of acute pelvic inflammatory disease. Obstet Gynecol 1990;75:867–872. [PubMed] [Google Scholar]
  • 28.Arredondo JLD. Oral clindamycin and ciprofloxacin versus intramuscular ceftriaxone and oral doxycycline in the treatment of mild-to-moderate pelvic inflammatory disease in outpatients. Clin Infect Dis 1997;24:170–178. [DOI] [PubMed] [Google Scholar]
  • 29.Landers DVW. Combination antimicrobial therapy in the treatment of acute pelvic inflammatory disease. Am J Obstet Gynecol 1991;164:849–858. [DOI] [PubMed] [Google Scholar]
  • 30.Martens MG, Gordon S, Yarborough DR, et al. Multicenter randomized trial of ofloxacin versus cefoxitin and doxycycline in outpatient treatment of pelvic inflammatory disease. Ambulatory PID Research Group. South Med J 1993;86:604–610. [DOI] [PubMed] [Google Scholar]
  • 31.Soper DE, Despres B, Soper DE, et al. A comparison of two antibiotic regimens for treatment of pelvic inflammatory disease. Obstet Gynecol 1988;72:7–12. [PubMed] [Google Scholar]
  • 32.American Society for Microbiology. Treatment of acute PID: Cefoxitin plus doxycycline versus clindamycin plus tobramycin. Minneapolis, Minnesota, Twenty fifth Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington DC: American Society for Microbiology; 29th October 1985. [Google Scholar]
  • 33.Wendel GD, Cox SM, Bawdon RE, et al. A randomized trial of ofloxacin versus cefoxitin and doxycycline in the outpatient treatment of acute salpingitis. Am J Obstet Gynecol 1991;164:1390–1396. [DOI] [PubMed] [Google Scholar]
  • 34.Apuzzio JJ, Stankiewicz R, Ganesh V, et al. Comparison of parenteral ciprofloxacin with clindamycin-gentamicin in the treatment of pelvic infection. Am J Med 1989;87:148S–151S. [DOI] [PubMed] [Google Scholar]
  • 35.Balbi G, Piscitelli V. Acute pelvic inflammatory disease: Compared therapeutical protocols. Minerva Ginecol 1996;48:19–23. [PubMed] [Google Scholar]
  • 36.Crombleholme WR, Schachter J, Ohm-Smith M, et al. Efficacy of single-agent therapy for the treatment of acute pelvic inflammatory disease with ciprofloxacin. Am J Med 1989;87:142S–147S. [DOI] [PubMed] [Google Scholar]
  • 37.Hemsell DL, Martens MG, Faro S, et al. A multicenter study comparing intravenous meropenem with clindamycin plus gentamicin for the treatment of acute gynecologic and obstetric pelvic infections in hospitalized women. Clin Infect Dis 1997;24 Suppl 2:S222–S230. [DOI] [PubMed] [Google Scholar]
  • 38.Larsen JW, Gabel-Hughes K, Kreter B, et al. Efficacy and tolerability of imipenem-cilastatin versus clindamycin+gentamicin for serious pelvic infections. Clin Ther 1992;14:90–96. [PubMed] [Google Scholar]
  • 39.Martens MG, Faro S, Hammill H, et al. Comparison of cefotaxime, cefoxitin and clindamycin plus gentamicin in the treatment of uncomplicated and complicated pelvic inflammatory disease. J Antimicrob Chemother 1990;26:37–43. [DOI] [PubMed] [Google Scholar]
  • 40.Thadepalli H, Mathai D, Scotti R, et al. Ciprofloxacin monotherapy for acute pelvic infections: a comparison with clindamycin plus gentamicin. Obstet Gynecol 1991;78:696–702. [PubMed] [Google Scholar]
  • 41.Buisson P, Mulard C, Baudet J, et al. [Treatment of upper genital infections in women. Multicenter study of the comparative efficacy and tolerance of an amoxicillin-clavulanic acid combination and of a triple antibiotic combination]. [French]. Rev Fr Gynecol Obstet 1989;84:699–703. [PubMed] [Google Scholar]
  • 42.Burchell HJ, Cronje HS, de Wet JI, et al. Efficacy of different antibiotics in the treatment of pelvic inflammatory disease. S Afr J Surg 1987;72:248–249. [PubMed] [Google Scholar]
  • 43.Ciraru-Vigneron N, Bercau G, Sauvanet E, et al. [The drug combination amoxicillin-clavulanic acid compared to the triple combination ampicillin-gentamicin-metronidazole in the treatment of severe adnexal infections]. [French]. Pathol Biol (Paris) 1986;34:665–668. [PubMed] [Google Scholar]
  • 44.De Beer JAA,V. Efficacy of ampicillin and cefoxitin in the treatment of acute pelvic inflammatory disease. A comparative study. S Afr J Surg 1983;64:733–735. [PubMed] [Google Scholar]
  • 45.Judlin P, Koebele A, Zaccabri A, et al. [Comparative study of ofloxacin+amoxicillin-clavulanic acid versus doxycycline+amoxicillin-clavulanic acid combination in the treatment of pelvic Chlamydia trachomatis infections]. [French]. J Gynecol Obstet Biol Reprod (Paris) 1995;24:253–259. [PubMed] [Google Scholar]
  • 46.Spence MRG. Randomized prospective comparison of ampicillin and doxycycline in the treatment of acute pelvic inflammatory disease in hospitalized patients. Sex Transm Dis 1981;8:164–166. [Google Scholar]
  • 47.Maggioni P, Di Stefano F, Facchini V, et al. Treatment of obstetric and gynecologic infections with meropenem: comparison with imipenem/cilastatin. J Chemother 1998;10:114–121. [DOI] [PubMed] [Google Scholar]
  • 48.Gjonnaess HDalaker. Treatment of pelvic inflammatory disease. Effects of lymecycline and clindamycine. Curr Ther Res Clin Exp 1981;29:885–892. [Google Scholar]
  • 49.Heinonen PKT. A comparison of ciprofloxacin with doxycycline plus metronidazole in the treatment of acute pelvic inflammatory disease. Scand J Infect Dis Suppl 1989;21:66–73. [PubMed] [Google Scholar]
  • 50.Walker CK, Kahn JG, Washington AE, et al. Pelvic inflammatory disease: metaanalysis of antimicrobial regimen efficacy. J Infect Dis 1993;168:969–978. Search date 1992; primary sources Medline, and bibliographies from reviews, textbooks, and references. [DOI] [PubMed] [Google Scholar]
  • 51.Walker CK, Workowski KA, Washington AE, et al. Anaerobes in pelvic inflammatory disease: implications for the Centers for Disease Control and Prevention's guidelines for treatment of sexually transmitted diseases. Clin Infect Dis 1999;28(suppl):29–36. Search date 1997; primary sources Medline, and bibliographies from reviews, textbooks, and references. [DOI] [PubMed] [Google Scholar]
  • 52.Ross JD, McCarthy G. United Kingdom national guidelines for the management of pelvic inflammatory disease 2011 (updated 2011). British Association for Sexual Health and HIV Clinical Effectiveness Group (BASHH). Available online at http://www.bashh.org/BASHH/Guidelines/Guidelines/BASHH/Guidelines/Guidelines.aspx (last accessed 1 November 2013). [Google Scholar]
  • 53.Soper DE, Brockwell NJ, Dalton HP. Microbial etiology of urban emergency department acute salpingitis: treatment with ofloxacin. Am J Obstet Gynecol 1992;167:653–660. [DOI] [PubMed] [Google Scholar]
  • 54.Buchan H, Vessey M, Goldacre M, et al. Morbidity following pelvic inflammatory disease. Br J Obstet Gynaecol 1993;100:558–562. [DOI] [PubMed] [Google Scholar]
  • 55.Brunham RC, Binns B, Guijon F, et al. Etiology and outcome of acute pelvic inflammatory disease. J Infect Dis 1988;158:510–517. [DOI] [PubMed] [Google Scholar]
  • 56.Story MJ, McCloud PI, Boehm G. Doxycycline tolerance study. Incidence of nausea after doxycycline administration to healthy volunteers: a comparison of 2 formulations (Doryx' vs Vibramycin'). Eur J Clin Pharmacol 1991;40:419–421. [DOI] [PubMed] [Google Scholar]
  • 57.Grimes DA, Schulz KF. Antibiotic prophylaxis for intrauterine contraceptive device insertion. In: The Cochrane Library, Issue 2, 2013. Chichester, UK: John Wiley & Sons, Ltd. Search date 2012. 11405986 [Google Scholar]
  • 58.Mohllajee AP, Curtis KM, Peterson HB. Does insertion and use of an intrauterine device increase the risk of pelvic inflammatory disease among women with sexually transmitted infection? A systematic review. Contraception 2006;73:145–153. [DOI] [PubMed] [Google Scholar]
BMJ Clin Evid. 2013 Dec 11;2013:1606.

Antibiotics for symptoms and microbiological clearance in women with confirmed pelvic inflammatory disease

Summary

There is consensus that antibiotic treatment is more effective than no treatment for women with confirmed PID.

Benefits and harms

Different antibiotics versus each other:

We found one systematic review (search date 2004, 34 RCTs, 3548 women) and four subsequent RCTs assessing the effects of different antibiotic regimens in the treatment of pelvic inflammatory disease (PID). The review assessed standard antibiotic regimens and non-standard regimens; see table 2 for 'standard' and 'non-standard' regimens, as defined by the review. The review identified no RCTs comparing standard or non-standard regimens versus placebo (see Comment section).

Table 1.

Standard antibiotic regimens and corresponding trial evidence (see text).

Regimen Trial evidence available
Oral ofloxacin 800 mg daily plus oral metronidazole 800 g daily for 14 days Ofloxacin plus metronidazole v clindamycin plus gentamicin
im ceftriaxone 250 mg once or im cefoxitin 2 g once plus oral probenecid 1 g once followed by oral doxycycline 200 mg daily plus oral metronidazole 800 mg daily for 14 days Cefoxitin plus doxycycline v cefoxitin plus probenecid plus doxycycline
im ceftriaxone 250 mg or im cefoxitin 2 g plus oral probenecid 1 g or a third-generation cephalosporin plus oral doxycycline 200 mg for 14 days Ceftriaxone or cefoxitin plus oral probenecid or a third-generation cephalosporin plus oral doxycycline v non-standard treatments
iv cefoxitin 6 g daily plus iv (or oral) doxycycline 200 mg daily followed by oral doxycycline 200 mg daily plus oral metronidazole 800 mg daily to complete 14 days Cefoxitin plus doxycycline v clindamycin plus gentamicin, cefoxitin plus doxycycline v cefoxitin plus probenecid plus doxycycline
iv clindamycin 2.7 g daily plus iv gentamicin 2 mg/kg loading dose then 4.5 mg/kg daily followed by either oral doxycycline 200 mg daily plus oral metronidazole 200 mg daily or oral clindamycin 1.8 g daily to complete 14 days Ofloxacin plus metronidazole v clindamycin plus gentamicin, cefoxitin plus doxycycline v clindamycin plus gentamicin, iv clindamycin plus gentamicin followed by either oral doxycycline plus oral metronidazole or oral clindamycin v non-standard treatments
iv ofloxacin 800 mg daily plus iv metronidazole 1.5 g daily for 14 days Ofloxacin plus metronidazole v clindamycin plus gentamicin
iv ciprofloxacin 400 mg daily plus iv (or oral) doxycycline 200 mg daily plus iv metronidazole 1.5 g daily (unspecified length, presume 14 days) No RCT comparisons
Open in a new tab

im, intramuscular; iv, intravenous

Cure rate

Different antibiotics compared with each other We don’t know how different antibiotic regimens compare with each other at improving cure rates in women with confirmed pelvic inflammatory disease (PID) (very low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Cure rate

RCT		 33 women
In review 		Cure rate
15/15 (100%) with ofloxacin (oral then IV) plus metronidazole
7/18 (39%) with clindamycin plus gentamicin
RR 1.06
95% CI 0.95 to 1.18
The review reported that overall trial quality was poor 		Not significant

RCT		 115 women
In review 		Cure rate
46/55 (84%) with cefoxitin plus doxycycline
52/60 (87%) with clindamycin plus gentamicin
RR 0.97
95% CI 0.83 to 1.12
The review reported that overall trial quality was poor 		Not significant

RCT		 198 women
In review 		Cure rate
75/94 (80%) with cefoxitin plus doxycycline
87/104 (84%) with clindamycin plus gentamicin
RR 0.95
95% CI 0.84 to 1.09
The review reported that overall trial quality was poor 		Not significant

RCT		 130 women
In review 		Cure rate
64/67 (96%) with cefoxitin plus doxycycline
57/63 (90%) with clindamycin plus gentamicin
RR 1.06
95% CI 0.96 to 1.16
Overall effect size
RR 1.01
95% CI 0.93 to 1.08
The review reported that overall trial quality was poor 		Not significant

RCT		 131 women
In review 		Cure rate
49/64 (77%) with ceftriaxone plus doxycycline
57/67 (85%) with ciprofloxacin plus clindamycin
RR 0.90
95% CI 0.76 to 1.07
The review reported that overall trial quality was poor 		Not significant

RCT		 148 women
In review 		Cure rate
73/75 (97%) with cefoxitin plus doxycycline
70/73 (96%) with clindamycin plus tobramycin
RR 1.02
95% CI 0.96 to 1.08
The review reported that overall trial quality was poor 		Not significant

RCT		 249 women
In review 		Cure rate
75/121 (62%) with cefoxitin plus probenecid plus doxycycline
80/128 (63%) with ofloxacin
RR 0.99
95% CI 0.82 to 1.20
The review reported that overall trial quality was poor 		Not significant

RCT		 62 women
In review 		Cure rate
30/31 (97%) with cefoxitin plus doxycycline
28/31 (90%) with clindamycin plus amikacin
RR 1.07
95% CI 0.94 to 1.22
The review reported that overall trial quality was poor 		Not significant

RCT		 79 women
In review 		Cure rate
38/40 (95%) with cefoxitin plus doxycycline
36/39 (92%) with clindamycin plus tobramycin
RR 1.03
95% CI 0.98 to 1.08
The review reported that overall trial quality was poor 		Not significant

RCT		 72 women
In review 		Cure rate
34/35 (97%) with cefoxitin plus probenecid plus doxycycline
35/37 (95%) with ofloxacin
RR 1.03
95% CI 0.93 to 1.13
Overall effect size
RR 1.02
95% CI 0.97 to 1.06
The review reported that overall trial quality was poor 		Not significant

RCT		 25 women
In review 		Cure rate
13/15 (87%) with clindamycin plus gentamicin
10/10 (100%) with ciprofloxacin
RR 0.87
95% CI 0.71 to 1.06
The review reported that overall trial quality was poor 		Not significant

RCT		 76 women
In review 		Cure rate
38/40 (95%) with clindamycin plus gentamicin
33/36 (92%) with ceftazidime plus doxycycline
RR 1.04
95% CI 0.92 to 1.17
The review reported that overall trial quality was poor 		Not significant

RCT		 68 women
In review 		Cure rate
34/35 (97%) with clindamycin plus gentamicin
33/33 (100%) with ciprofloxacin (plus clindamycin in one women)
RR 0.97
95% CI 0.92 to 1.03
The review reported that overall trial quality was poor 		Not significant

RCT		 84 women
In review 		Cure rate
40/40 (100%) with clindamycin plus gentamicin
41/44 (93%) with meropenem
RR 1.07
95% CI 0.99 to 1.16
The review reported that overall trial quality was poor 		Not significant

RCT		 77 women
In review 		Cure rate
39/40 (98%) with clindamycin plus gentamicin plus doxycycline
37/37 (100%) with imipenem plus cilastin (plus doxycycline in some women)
RR 0.98
95% CI 0.93 to 1.02
The review reported that overall trial quality was poor 		Not significant

RCT		 58 women
In review 		Cure rate
21/29 (72%) with clindamycin plus gentamicin
23/29 (79%) with cefotaxime
RR 0.91
95% CI 0.68 to 1.22
The review reported that overall trial quality was poor 		Not significant

RCT		 30 women
In review 		Cure rate
14/14 (100%) with clindamycin plus gentamicin
15/16 (94%) with ciprofloxacin
RR 0.98
95% CI 0.90 to 1.07
Overall effect size
RR 1.00
95% CI 0.96 to 1.04
The review reported that overall trial quality was poor 		Not significant

RCT		 81 women
In review 		Cure rate
10/42 (24%) with amoxicillin/clavulanate
9/39 (25%) with amoxicillin plus aminoglycoside plus metronidazole
RR 1.03
95% CI 0.47 to 2.27
The review reported that overall trial quality was poor 		Not significant

RCT		 20 women
In review 		Cure rate
2/10 (20%) with ampicillin plus metronidazole
10/10 (100%) with doxycycline plus oxytetracycline/tetracycline plus metronidazole
RR 0.20
95% CI 0.06 to 0.69
The review reported that overall trial quality was poor 		Large effect size doxycycline plus oxytetracycline/tetracycline plus metronidazole

RCT		 44 women
In review 		Cure rate
20/22 (91%) with amoxicillin/clavulanate
19/22 (86%) with ampicillin (or amoxicillin) plus gentamicin plus metronidazole
RR 1.05
95% CI 0.85 to 1.30
The review reported that overall trial quality was poor 		Not significant

RCT		 60 women
In review 		Cure rate
28/30 (93%) with ampicillin
28/30 (93%) with cefoxitin
RR 1.00
95% CI 0.87 to 1.14
The review reported that overall trial quality was poor 		Not significant

RCT		 33 women
In review 		Cure rate
17/18 (94%) with doxycycline plus amoxicillin/clavulanate
15/15 (100%) with ofloxacin plus amoxicillin/clavulanate
RR 0.94
95% CI 0.84 to 1.06
The review reported that overall trial quality was poor 		Not significant

RCT		 47 women
In review 		Cure rate
22/23 (97%) with ampicillin
18/24 (75%) with doxycycline
RR 1.28
95% CI 1.00 to 1.63
Overall effect size
RR 1.05
95% CI 0.91 to 1.22
The review reported that overall trial quality was poor 		Not significant

RCT		 34 women
In review 		Cure rate
14/16 (88%) with imipenem plus cilastatin
18/18 (100%) with meropenem
RR 0.88
95% CI 0.73 to 1.05
The review reported that overall trial quality was poor 		Not significant

RCT		 36 women
In review 		Cure rate
16/19 (84%) with cefoxitin
14/17 (82%) with cefotaxime
RR 1.02
95% CI 0.76 to 1.37
Overall effect size
RR 0.95
95% CI 0.87 to 1.04
The review reported that overall trial quality was poor 		Not significant

RCT		 64 women
In review 		Cure rate
42/44 (95%) with lymecycline
9/20 (45%) with clindamycin
RR 2.12
95% CI 1.30 to 3.46
The review reported that overall trial quality was poor 		Moderate effect size lymecycline

RCT		 79 women
In review 		Cure rate
40/40 (100%) with azithromycin plus metronidazole
38/39 (97%) with azithromycin
RR 0.89
95% CI 0.50 to 1.57
The review reported that overall trial quality was poor 		Not significant

RCT		 36 women
In review 		Cure rate
14/20 (70%) with doxycycline plus metronidazole
15/16 (94%) with ciprofloxacin
RR 0.75
95% CI 0.55 to 1.02
Overall effect size
RR 0.80
95% CI 0.52 to 1.24
The review reported that overall trial quality was poor 		Not significant

RCT		 741 women with PID, without pelvic or tubo-ovarian abscess Resolution of signs and symptoms 5–24 days post-treatment
262/289 (90.7%) with ofloxacin plus metronidazole
248/275 (90.2%) with moxifloxacin alone
Difference +0.5%
95% CI –5.7% to +4.0%
The review reported that overall trial quality was poor 		Not significant

RCT		 669 women with uncomplicated acute PID Clinical cure rate (defined as reduction of ≥70% in severity score and normal temperature and leukocyte count) 2–14 days post-treatment
222/342 (64.7%) with oral moxifloxacin for 14 days
212/326 (65%) with oral doxycycline plus oral metronidazole for 14 days plus one oral ciprofloxacin dose
P >0.05 		Not significant

RCT		 669 women with uncomplicated acute PID Clinical success rate (defined as clinical cure or improvement i.e., <70% reduction but >30% plus normal temperature and leukocyte count) 21–35 days post-treatment
206/343 (60%) with oral moxifloxacin for 14 days
191/326 (59%) with oral doxycycline plus oral metronidazole for 14 days plus one oral ciprofloxacin dose
P >0.05 		Not significant

RCT		 120 women with mild PID treated in an outpatient setting Cure rate (defined as absence or reduction of pelvic tenderness as compared to baseline pain levels) day 14
42/58 (72%) with doxycycline
56/62 (90%) with azithromycin plus placebo
P = 0.01 		azithromycin

RCT		 120 women with mild PID treated in an outpatient setting Cure rate (defined as reduction of >70% on VAS) day 14
23/42 (55%) with doxycycline
35/56 (63%) with azithromycin plus placebo
P = 0.53 		Not significant

RCT		 120 women with mild PID treated in an outpatient setting Cure rate (defined as reduction of >70% on modified McCormack pain scale) day 14
13/42 (31%) with doxycycline
21/56 (38%) with azithromycin plus placebo
P = 0.52 		Not significant

RCT		 460 women with PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination, not requiring intravenous treatment Clinical cure rate (>70% reduction in tenderness score on McCormack scale, apyrexia, and WBC <10,500/mm3) 7–14 days post-treatment
163/228 (71.5%) with oral moxifloxacin for 14 days
171/232 (73.7%) with oral levofloxacin plus oral metronidazole for 14 days
P >0.05 		Not significant

RCT		 460 women with PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination, not requiring intravenous treatment Clinical cure rate (>70% reduction in tenderness score on McCormack scale, apyrexia, and WBC <10,500/mm3) 28–42 days post-treatment
166/228 (72.8%) with oral moxifloxacin for 14 days
169/232 (72.8%) with oral levofloxacin plus oral metronidazole for 14 days
Significance not assessed
Open in a new tab

Symptom severity

Different antibiotics compared with each other We don’t know how different antibiotic regimens compare with each other at reducing symptoms in women with mild PID (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom severity

RCT		 120 women with mild PID treated in an outpatient setting Median VAS pain score (range 0–10) day 14
0.8 with doxycycline
0.4 with azithromycin plus placebo
P = 0.23 		Not significant

RCT		 120 women with mild PID treated in an outpatient setting Median McCormack pain score (range 0–3, total score defined as the sum of individual scores for 12 abdominal and pelvic regions [maximum score = 36]) day 14
4 with doxycycline
3 with azithromycin plus placebo
P = 0.59 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Rate of ectopic pregnancy

No data from the following reference on this outcome.

Fertility

No data from the following reference on this outcome.

Recurrence

Different antibiotics compared with each other We don’t know how effective oral moxifloxacin and oral levofloxacin plus oral metronidazole are, compared with each other, at improving recurrence rates at 28–42 days post-treatment in women with confirmed PID (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Recurrence

RCT		 460 women with PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination, not requiring intravenous treatment Clinical recurrence/relapse (defined as reappearance of signs and symptoms of PID) 28–42 days post-treatment
18/228 (7.9%) with oral moxifloxacin for 14 days
19/232 (8.2%) with oral levofloxacin plus oral metronidazole for 14 days
Significance not assessed
Open in a new tab

No data from the following reference on this outcome.

Rate of transmission to others

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects (global)

RCT		 138 women
In review 		Adverse effect (any)
52/69 (75%) with ceftriaxone plus doxycycline
57/69 (83%) with ciprofloxacin plus clindamycin
Significance not assessed

RCT		 272 women
In review 		Adverse effects (any)
20/134 (15%) with cefoxitin plus probenecid plus doxycycline
9/138 (7%) with ofloxacin
Significance not assessed

RCT		 72 women
In review 		Adverse effects (any)
9/35 (26%) with cefoxitin plus probenecid plus doxycycline
6/37 (26%) with ofloxacin
Significance not assessed

RCT		 81 women
In review 		Adverse effect (any)
5/42 (12%) with amoxicillin/clavulanate
2/39 (5%) with amoxicillin plus aminoglycoside plus metronidazole
Significance not assessed

RCT		 36 women
In review 		Adverse effect (any)
11/20 (55%) with doxycycline
3/16 (19%) with metronidazole
Significance not assessed

RCT		 213 women
In review 		Adverse effect (any)
32/107 (30%) with azithromycin plus metronidazole
26/106 (25%) with azithromycin
Significance not assessed

RCT		 170 women
In review 		Vestibular disturbance
0/82 (0%) with cefoxitin plus doxycycline
3/88 (3%) with clindamycin plus gentamicin
Significance not assessed

RCT		 120 women
In review 		Surgical intervention
1/60 (2%) with cefoxitin plus doxycycline
1/60 (2%) with clindamycin plus gentamicin
Significance not assessed

RCT		 669 women with uncomplicated acute PID Incidence of drug-related adverse event 2–14 days post-treatment
151/343 (44%) with oral moxifloxacin for 14 days
162/326 (50%) with oral doxycycline for 14 days plus one oral ciprofloxacin dose
P = 0.14 		Not significant
Withdrawal from treatment owing to adverse effects

RCT		 138 women
In review 		Withdrawal from treatment
1/69 (1%) with ceftriaxone plus doxycycline
1/69 (1%) with ciprofloxacin plus clindamycin
Significance not assessed

RCT		 80 women
In review 		Withdrew from study
0/40 (0%) with clindamycin plus gentamicin
0/40 (0%) with ceftazidime plus doxycycline
Significance not assessed

RCT		 120 women
In review 		Withdrew from study due to adverse effects
0/60 (0%) with cefoxitin plus doxycycline
1/60 (2%) with clindamycin plus gentamicin
Significance not assessed

RCT		 230 women
In review 		Withdrew from study due to adverse effects
1/114 (1%) with cefoxitin plus doxycycline
0/116 (0%) with clindamycin plus gentamicin
Significance not assessed

RCT		 81 women
In review 		Withdrawal from treatment due to adverse effects
0/42 (0%) with amoxicillin/clavulanate
1/39 (3%) with amoxicillin plus aminoglycoside plus metronidazole
Significance not assessed

RCT		 33 people
In review 		Withdrawal from treatment due to adverse effects
0/15 (0%) with amoxicillin/clavulanate
0/18 (0%) with ofloxacin
Significance not assessed

RCT		 36 women
In review 		Withdrawal from treatment due to adverse effects
0/20 (0%) with doxycycline
0/16 (0%) with metronidazole
Significance not assessed

RCT		 213 women
In review 		Withdrawn from treatment due to adverse effects
4/107 (4%) with azithromycin plus metronidazole
2/106 (2%) with azithromycin
Significance not assessed

RCT		 460 women with PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination, not requiring intravenous treatment Withdrawn from treatment due to at least 1 drug-related event
4% with oral moxifloxacin for 14 days
5% with oral levofloxacin plus oral metronidazole for 14 days
Significance not assessed
Angio-oedema

RCT		 81 women
In review 		Angio-oedema
0/42 (0%) with amoxicillin/clavulanate
1/39 (3%) with amoxicillin plus aminoglycoside plus metronidazole
Significance not assessed
Allergy

RCT		 148 women
In review 		Rash
2/75 (3%) with cefoxitin plus doxycycline
1/75 (1%) with clindamycin plus tobramycin
Significance not assessed

RCT		 272 women
In review 		Rash
1/134 (0.7%) with cefoxitin plus probenecid plus doxycycline
2/138 (1.4%) with ofloxacin
Significance not assessed

RCT		 669 women with uncomplicated acute PID Incidence of drug-related rash 2–14 days post-treatment
8/343 (2%) with oral moxifloxacin for 14 days
10/326 (3%) with oral doxycyline plus oral metronidazole for 14 days plus one oral ciprofaloxacin dose
Significance not assessed

RCT		 130 women
In review 		Mild rash
1/67(2%) with cefoxitin pus doxycycline
1/63 (2%) with clindamycin plus gentamicin
Significance not assessed

RCT		 72 women
In review 		Allergy
0/35 (0%) with cefoxitin plus probenecid plus doxycycline
1/37 (3%) with ofloxacin
Significance not assessed

RCT		 70 women
In review 		Allergies
0/35 (0%) with clindamycin plus gentamicin
2/35 (6%) with ciprofloxacin (plus clindamycin in 1 woman)
Significance not assessed

RCT		 44 women
In review 		Cutaneous allergy
1/22 (5%) with amoxicillin/clavulanate
0/22 (0%) with ampicillin (or amoxicillin) plus gentamicin plus metronidazole
Significance not assessed

RCT		 230 women
In review 		Pruritus
2/114 (2%) with cefoxitin plus doxycycline
11/116 (9%) with clindamycin plus gentamicin
Significance not assessed
Gastrointestinal

RCT		 170 women
In review 		Gastrointestinal
10/82 (12%) with cefoxitin plus doxycycline
15/88 (17%) with clindamycin plus gentamicin
Significance not assessed

RCT		 741 women Gastrointestinal
54/378 (14%) with moxifloxacin
71/363 (20%) with ofloxacin plus metronidazole
P = 0.057 		Not significant

RCT		 669 women with uncomplicated acute PID Incidence of any drug-related gastro-intestinal adverse events 2–14 days post-treatment
100/343 (29%) with oral moxifloxacin for 14 days
149/326 (46%) with oral doxycycline plus oral metronidazole for 14 days plus one oral ciprofloxacin dose
P = 0.001 		oral moxifloxacin

RCT		 130 women
In review 		Diarrhoea
2/67 (3%) with cefoxitin plus doxycycline
2/63 (3%) with clindamycin plus gentamicin
Significance not assessed

RCT		 669 women with uncomplicated acute PID Incidence of any drug-related diarrhoea 2–14 days post-treatment
26/343 (8%) with oral moxifloxacin for 14 days
24/326 (7%) with oral doxycycline plus oral metronidazole for 14 days plus one oral ciprofloxacin dose
Significance not assessed

RCT		 460 women with PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination, not requiring intravenous treatment Incidence of nausea 28–42 days post-treatment
42/228 (18.7%) with oral moxifloxacin for 14 days
53/232 (23%) with oral levofloxacin plus oral metronidazole for 14 days
Significance not assessed

RCT		 272 women
In review 		Nausea/vomiting
19/134 (14%) with cefoxitin plus probenecid plus doxycycline
2/138 (1%) with ofloxacin
Significance not assessed

RCT		 72 women
In review 		Nausea/vomiting
3/35 (9%) with cefoxitin plus probenecid plus doxycycline
2/37 (5%) with ofloxacin
Significance not assessed

RCT		 669 women with uncomplicated acute PID Incidence of drug-related nausea 2–14 days post-treatment
57/343 (17%) with oral moxifloxacin for 14 days
79/326 (24%) with oral doxycycline plus oral metronidazole for 14 days plus one oral ciprofloxacin dose
Significance not assessed

RCT		 669 women with uncomplicated acute PID Incidence of drug-related vomiting 2–14 days post-treatment
13/343 (4%) with oral moxifloxacin for 14 days
36/326 (11%) with oral doxycycline plus oral metronidazole for 14 days plus one oral ciprofloxacin dose
Significance not assessed

RCT		 460 women with PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination, not requiring intravenous treatment Incidence of vomiting 28–42 days post-treatment
6/228 (2.7%) with oral moxifloxacin for 14 days
15/232 (6.5%) with oral levofloxacin plus oral metronidazole for 14 days
Significance not assessed

RCT		 460 women with PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination, not requiring intravenous treatment Incidence of upper abdominal pain 28–42 days post-treatment
9/228 (4%) with oral moxifloxacin for 14 days
13/232 (5.7%) with oral levofloxacin plus oral metronidazole for 14 days
Significance not assessed
Headaches/insomnia

RCT		 272 women
In review 		Insomnia
0/134 (0%) with cefoxitin plus probenecid plus doxycycline
2/138 (1%) with ofloxacin
Significance not assessed

RCT		 72 women
In review 		Headaches
0/35 (0%) with cefoxitin plus probenecid plus doxycycline
1/37 (3%) with ofloxacin
Significance not assessed
Candidal vaginitis

RCT		 272 women
In review 		Candidal vaginitis
6/134 (4%) with cefoxitin plus probenecid plus doxycycline
5/138 (4%) with ofloxacin
Significance not assessed

RCT		 72 women
In review 		Candidal vaginitis
2/35 (6%) with cefoxitin plus probenecid plus doxycycline
1/37 (3%) with ofloxacin
Significance not assessed
Severe adverse effects

RCT		 213 women
In review 		Severe adverse effects
8/107 (7%) with azithromycin plus metronidazole
2/106 (2%) with azithromycin
Significance not assessed

RCT		 460 women with PID with no pelvic or tubo-ovarian abscess on pelvic ultrasonography and at laparoscopic examination, not requiring intravenous treatment Incidence of serious adverse events 28–42 days post-treatment
3/228 (1.3%) with oral moxifloxacin for 14 days
1/232 (0.4%) with oral levofloxacin plus oral metronidazole for 14 days
Significance not assessed
Open in a new tab

No data from the following reference on this outcome.

Further information on studies

The review included women who had been either: diagnosed clinically or laparoscopically with PID; treated with any antibiotic combination; and with an outcome measure of clinical care, microbiological care, infertility, ectopic pregnancy, chronic pelvic pain, or any other relevant outcome. The review made no distinction for severity of disease or between intravenous and oral treatment.

Comment

We found one systematic review (search date 1992, 21 studies), which reported on clinical and microbiological cure rates for various antibiotic regimens in the treatment of pelvic inflammatory disease (PID; see table 3 ). The review provided aggregated data on indirect comparisons; aspects of the review were subsequently updated (search date 1997, 26 studies, 1925 women). The earlier version of the review examined all antimicrobial regimens, whereas the updated version focused on anti-anaerobic treatment. The identified studies included case series, and it is not possible to ascertain from the aggregated data published how many studies were RCTs. Inclusion criteria were a diagnosis of PID (clinical, microbiological, laparoscopic, or by endometrial biopsy) and microbiological testing for Chlamydia trachomatis and Neisseria gonorrhoeae. The review found that antibiotics were effective in relieving the symptoms associated with PID, with clinical and microbiological cure rates of 88% to 100% (see table 2 ). The only regimen that seemed to perform less well was oral metronidazole plus doxycycline. However, the studies were of low power, and apparent differences in efficacy may have been confounded by differences in disease severity among studies.

Table 1.

Cure rates for the antibiotic treatment of acute PID: aggregated data from a systematic review of RCTs and case series (see text).

Drug regimen Number of studies Number of women Cure rate (%)
      Clinical Microbiological*
Inpatient treatment (initially parenteral switching to oral)
Clindamycin plus aminoglycoside 11 470 91 97
Cefoxitin plus doxycycline 8 427 91 98
Cefotetan plus doxycycline 3 174 95 100
Ceftizoxime plus tetracycline 1 18 88 100
Cefotaxime plus tetracycline 1 19 94 100
Ciprofloxacin 4 90 94 96
Ofloxacin 1 36 100 97
Sulbactam/ampicillin plus doxycycline 1 37 95 100
Co-amoxiclav 1 32 93 –
Metronidazole plus doxycycline 2 36 75 71
Outpatient treatment (oral unless indicated otherwise)
Cefoxitin (im) plus probenecid plus doxycycline 3 219 89 93
Ofloxacin 2 165 95 100
Co-amoxiclav 1 35 100 100
Sulbactam/ampicillin 1 36 70 70
Ceftriaxone (im) plus doxycycline 1 64 95 100
Ciprofloxacin plus clindamycin 1 67 97 94
Open in a new tab

*Neisseria gonorrhoeae, Chlamydia trachomatis, or both, when detected in lower genital tract; im, intramuscular; PID, pelvic inflammatory disease

Clinical guide:

We found no RCTs comparing antibiotics versus placebo or no treatment. However, such trials would be considered unethical because there is strong consensus that antibiotic treatments are more effective in women with pelvic inflammatory disease (PID) than no treatment. We found little evidence about treatment of PID of differing severity, the effect of ethnicity, or the effects of tracing sexual contacts (see review on Partner notification). The risks of tubal occlusion and of subsequent infertility relate to the severity of PID before starting treatment. Clinical improvement may not translate into preserved fertility. The inclusion of observational studies in the older systematic review without a sensitivity analysis may compromise the validity of the conclusions. In the review, reliable comparison of different drugs may be confounded by possible differences in disease severity among the included studies.

Substantive changes

Antibiotics (for symptoms and microbiological clearance in women with confirmed pelvic inflammatory disease) Three RCTs added; categorisation unchanged (likely to be beneficial).

BMJ Clin Evid. 2013 Dec 11;2013:1606.

Oral antibiotics versus parenteral antibiotics

Summary

Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility in women with mild to moderate PID, with fewer adverse effects. However, we don't know the optimal duration of treatment.

Benefits and harms

Oral antibiotics versus parenteral antibiotics:

We found one systematic review containing three RCTs that compared oral versus parenteral antibiotic treatment.

Cure rate

Oral antibiotics compared with parenteral antibiotics Oral antibiotics and parenteral antibiotics may be equally effective at improving cure rate in women with uncomplicated PID (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Cure rate

RCT		 249 women with uncomplicated pelvic inflammatory disease (outpatient setting)
In review 		Cure rate
with oral ofloxacin
with parenteral cefoxitin plus oral doxycycline
Absolute results not reported
RR 1.03
95% CI 0.97 to 1.10 		Not significant

RCT		 72 women with uncomplicated acute salpingitis (outpatient setting)
In review 		Cure rate
with oral ofloxacin
with parenteral cefoxitin plus oral doxycycline
Absolute results not reported
RR 0.97
95% CI 0.88 to 1.07 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Symptom severity

Oral antibiotics compared with parenteral antibiotics Oral antibiotics (given as an outpatient treatment) and parenteral antibiotics (given as an inpatient treatment) may be equally effective at improving tenderness, chronic pelvic pain, and endometriosis in women with mild to moderate PID (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Symptom severity
831 women with mild to moderate PID
In review 		Tender on exam 30 days
69/335 (21%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
63/324 (18%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
P = 0.50 		Not significant

RCT		 831 women with mild to moderate PID
In review 		Endometritis (on biopsy) 30 days
102/222 (46%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
85/226 (38%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
P = 0.09 		Not significant

RCT		 831 women with mild to moderate PID
In review 		Tubo-ovarian abscess 30 days
4/410 (0.9%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
12/398 (0.7%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
Significance not assessed

RCT		 831 women with mild to moderate PID
In review 		Chronic pelvic pain 35 months
128/380 (34%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
110/369 (30%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
OR 1.24
95% CI 0.87 to 1.77 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Rate of ectopic pregnancy

Oral antibiotics compared with parenteral antibiotics Oral antibiotics (given as an outpatient treatment) and parenteral antibiotics (given as an inpatient treatment) are equally effective at reducing rate of ectopic pregnancy in women with mild to moderate PID (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Rate of ectopic pregnancy

RCT		 831 women with mild to moderate PID
In review 		Ectopic pregnancy 35 months
4/410 (1%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
1/398 (0.3%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
OR 3.66
95% CI 0.40 to 33.12 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Fertility

Oral antibiotics compared with parenteral antibiotics Oral antibiotics (given as an outpatient treatment) and parenteral antibiotics (given as an inpatient treatment) may be equally effective at improving pregnancy or reducing infertility at 35 months in women with mild to moderate PID (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Pregnancy

RCT		 831 women with mild to moderate PID
In review 		Pregnancy 35 months
174/410 (42%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
166/398 (42%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
Significance not assessed
Infertility

RCT		 831 women with mild to moderate PID
In review 		Infertility 35 months
71/385 (18.4%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
67/347 (17.9%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
OR 1.32
95% CI 0.86 to 2.04 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Recurrence

Oral antibiotics compared with parenteral antibiotics Oral antibiotics (given as an outpatient treatment) and parenteral antibiotics (given as an inpatient treatment) may be equally effective at reducing recurrence of PID at 35 months (low-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Recurrence

RCT		 831 women with mild to moderate PID
In review 		Recurrent PID 35 months
51/410 (12%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
66/398 (17%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
OR 0.69
95% CI 0.43 to 1.09 		Not significant
Open in a new tab

No data from the following reference on this outcome.

Rate of transmission to others

No data from the following reference on this outcome.

Quality of life

No data from the following reference on this outcome.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

RCT		 249 women with uncomplicated pelvic inflammatory disease
In review 		Adverse effects
7% with oral ofloxacin
15% with parenteral cefoxitin plus oral doxycycline
Absolute numbers not reported
P <0.2 		Not significant

RCT		 72 women with uncomplicated acute salpingitis
In review 		Adverse effects
16% with oral ofloxacin
26% with parenteral cefoxitin plus oral doxycycline
Absolute numbers not reported
Significance not assessed

RCT		 831 women with mild to moderate PID
In review 		Adverse drug reaction
7/410 (1.7%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
6/398 (1.5%) with admission for parenteral antibiotics (inpatient)
Significance not assessed

RCT		 831 women with mild to moderate PID
In review 		Phlebitis 30 days
0/410 (0%) with single intramuscular dose of cefoxitin plus oral probenecid followed by oral doxycycline (outpatient)
14/398 (3%) with IV cefoxitin plus IV doxycycline followed by oral doxycycline (hospital admission for parenteral antibiotics; inpatient)
Significance not assessed
Open in a new tab

Comment

Clinical guide:

Parenteral administration is indicated in people with severe PID (i.e., those with severe systemic symptoms or tubo-ovarian abscess), those who cannot tolerate fluids orally, and those with any other factor for hospitalisation (e.g., diagnostic uncertainty, pregnant or adolescent people, when severe disease precludes outpatient management, in people unable to follow or tolerate an outpatient regimen, in people who have not responded to outpatient therapy, when clinical follow-up cannot be arranged).

Parenteral treatment as an inpatient offers no advantage over outpatient treatment in women with mild-to-moderate pelvic inflammatory disease (defined as the absence of a tubo-ovarian abscess).

Substantive changes

No new evidence

BMJ Clin Evid. 2013 Dec 11;2013:1606.

Different durations of antibiotic treatment

Summary

We found no direct information about optimal durations of antibiotic treatment in women with PID. A 14-day treatment course is currently recommended.

Benefits and harms

Different durations of antibiotics versus each other:

We identified two systematic reviews that assessed the effects of different antibiotic regimens in the treatment of PID. Neither review assessed the effect of duration of treatment on clinical outcomes, although the most common treatment period was 14 days.

Adverse effects

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Adverse effects

Systematic review		 Number of people not reported Adverse effects 2 weeks
with metronidazole plus doxycycline
Open in a new tab

No data from the following reference on this outcome.

Comment

Clinical guide:

A 14-day treatment course is recommended for pelvic inflammatory disease based on the current evidence.

Substantive changes

No new evidence

BMJ Clin Evid. 2013 Dec 11;2013:1606.

Routine antibiotic prophylaxis before IUD insertion in women at high risk

Summary

We found no direct information from RCTs about antibiotic prophylaxis before IUD insertion in women at high risk of pelvic inflammatory disease.

Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable, but we don't know whether prophylactic antibiotics before IUD insertion reduce these risks.

Benefits and harms

Antibiotic prophylaxis before IUD insertion in women at high risk:

We found no RCTs on the effects of routine antibiotic prophylaxis in women at high risk of pelvic inflammatory disease.

Comment

Nausea and vomiting has been reported with 17% to 28% of healthy volunteers on doxycycline, depending on the formulation given.

See the harms section of Antibiotics (for symptoms and microbiological clearance in women with confirmed pelvic inflammatory disease).

Substantive changes

No new evidence

BMJ Clin Evid. 2013 Dec 11;2013:1606.

Routine antibiotic prophylaxis before IUD insertion in women at low risk

Summary

Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable, but prophylactic antibiotics in women at low risk of PID seem no more effective than placebo at reducing rate of PID.

Benefits and harms

Antibiotic prophylaxis before IUD insertion versus no antibiotic prophylaxis (in women at low risk):

We found one systematic review (search date 2012, 6 RCTs, 5797 women requesting IUD insertion).

Rate of PID

Antibiotic prophylaxis before IUD insertion versus no antibiotic prophylaxis (in women at low risk) Antibiotic prophylaxis before IUD insertion seems no more effective than placebo or no treatment at reducing the incidence of pelvic inflammatory disease in women at low risk of PID (moderate-quality evidence).

Ref (type) Population Outcome, Interventions Results and statistical analysis Effect size Favours
Rate of PID

Systematic review		 5797 women requesting IUD insertion
6 RCTs in this analysis		 Incidence of PID
27/2906 (0.9%) with single dose of doxycycline or azithromycin (1 hour before IUD insertion)
30/2891 (1.0%) with placebo (1 hour before IUD insertion) or no treatment
RR 0.89
95% CI 0.53 to 1.50
The wide confidence interval suggests that the study may have lacked power to detect a clinically important difference 		Not significant
Open in a new tab

Further information on studies

None.

Comment

Nausea and vomiting has been reported with 17% to 28% of healthy volunteers on doxycycline, depending on the formulation given.

See the harms section of Antibiotics (for symptoms and microbiological clearance in women with confirmed pelvic inflammatory disease).

Clinical guide:

In the populations included in the systematic review, the risk of PID after IUD insertion was low. The occurrence of PID in this group usually reflects the introduction of infection into the uterus during IUD insertion, and will therefore vary with the prevalence of STDs in the population. A further systematic review also found that the absolute risk of PID was low even when gonorrhoea or chlamydia was present at the time of IUD insertion (0%–5% for those with an STD compared with 0%–2% in those without an STD).

Substantive changes

Routine antibiotic prophylaxis before IUD insertion in women at low risk One previously included systematic review updated and new data added. Categorisation unchanged (unlikely to be beneficial).

Articles from BMJ Clinical Evidence are provided here courtesy of BMJ Publishing Group

RESOURCES